The primary amino acid sequence of the human enzyme, hypoxanthine-guanine phosphoribosyl transferase will be determined by conventional procedures including specific chemical cleavage of subunits, enzymatic digestion, Edman degradation, and amino acid analysis. The biochemical basis for genetic variation of the enzyme will be studied, with primary emphasis on those variants involved in certain types of gout and in Lesch-Nyhan's disease, an inborn error of metabolism. Chemically induced variants will also be studied: variant enzyme in all cases will be purified from lymphoblastoid cell lines by affinity chromatography. Phosphoribosyl transferases from other species will be examined in an attempt to elucidate the relationship between enzyme structure and catalytic function, using chemical modifications of specific amino acids, as well as sequence data. Finally, the molecular basis for neurological dysfunction as a result of very low hypoxanthine-guanine phosphoribosyl transferase activity, as well as the role of the enzyme in purine metabolism, will be investigated through genetic and embryological studies.